The objective of the proposed research is to use computer-assisted quantitative cytologic techniques in an attempt to define the nature and locus of structural abnormalities of Golgi-impregnated nerve cells in a variety of human neuropsychiatric diseases, especially schizophrenia and unclassified mental retardation syndromes. Traditionally neuropathologic analysis of these disorders has not disclosed consistent or unequivocal structural changes. It is possible that significant changes are present but beyond the resolution of the relatively crude qualitative methods employed to date. These disorders are characterized clinically by abnormalities of cognition and behavior presumably reflecting disordered function of forebrain cortical structures. Our working hypothesis is that they may also be associated, at least at some level, with abnormalities of the structure and organization of cortical neurons. We propose to examine the structure of individual cortical neurons, as revealed by Golgi impregnations, using computer assisted quantitative morphologic techniques. Strategies for morphormetric analysis of Golgi impregnated neurons will be developed and tested first in laboratory mice. Principles derived from analysis of normal neurons will be tested in animal models of neurologic disease to determine the nature and specificity of structural change in response to a variety of pathological insults. Results from animal studies will provide the conceptual basis for interpreting changes encountered in Golgi impregnated cortical neurons from cases of neuropsychiatric disease. If successful, abnormalities identified in this way provide new insights into the pathophysiology of nerve cell malfunction in these disorders.